Tumor virus SV40 provides an opportunity for the study of the role of single genes in the initiation and maintenance of neoplastic cell transformation. Studies with temperature-sensitive mutants have identified the A gene that is required for both productive and transforming infection. In productive infection, the A gene regulates viral DNA replication and transcription. In transforming infection, it is required to initiate and possibly to maintain the new growth characteristics of cells. We have identified the A protein and are studying its function using nucleoprotein complexes. We are purifying wild-type and mutant A proteins to investigate their function in vitro. Studies with deletion mutants show that the early region of the SV40 genome codes for at least two unique proteins in addition to the A protein: One of these is known to be required for transformation. The functions of the two newly discovered proteins in productive infections is unknown. The interaction of the proteins with cellular components will be investigated.